Experimental oral treatment quickly controls HAE attacks in Phase 3 trial
Deucrictibant IR also significantly reduced need for rescue medication
Written by |
A single oral dose of the experimental treatment deucrictibant rapidly brought hereditary angioedema (HAE) attacks under control, significantly shortening the time to symptom relief, stopping attacks from worsening sooner, and speeding complete symptom resolution compared with a placebo.
That’s according to results from the now-completed Phase 3 RAPIDe-3 trial (NCT06343779). The trial compared the safety and efficacy of the 20 mg immediate-release (IR) deucrictibant capsule, which is being developed by Pharvaris to treat HAE attacks as they occur, against a placebo in 134 people with HAE. It was conducted at 59 sites across 24 countries.
Deucrictibant IR also significantly reduced the need for rescue medication, with most attacks managed with a single capsule. No treatment-related severe or serious adverse events occurred. According to the company, RAPIDe-3 met its primary goal and all secondary goals.
“The results of the RAPIDe-3 study demonstrate that deucrictibant IR … rapidly ended attack progression and accelerated the time to complete symptom resolution,” Marc Riedl, MD, the study’s lead author and a professor of medicine at the University of California, San Diego, said in a company press release.
The trial’s findings were detailed in the study, “Oral deucrictibant for on-demand treatment of hereditary angioedema attacks: a phase 3, multicentre, randomised, double-blind, placebo-controlled crossover trial,” which was published in The Lancet.
Deucrictibant IR could help control attacks across different HAE types
HAE is caused by genetic mutations that lead to excessive production of bradykinin, a signaling molecule that causes blood vessels to widen and leak fluid into surrounding tissues. This triggers unpredictable swelling attacks that can affect the abdomen, limbs, face, and airways.
In HAE type 1, these mutations reduce the levels of C1 inhibitor (C1-INH), a protein that helps regulate bradykinin production. In HAE type 2, the protein is present but does not work properly, while the rarer HAE type 3 occurs despite normal C1-INH levels and function.
On-demand treatments help bring attacks under control. Although oral options are available, most approved on-demand HAE therapies require injections under the skin or into a vein, which can make them less convenient to use and potentially delay treatment.
Deucrictibant IR is being developed as another oral option alongside the approved therapy Ekterly (sebetralstat). Unlike Ekterly, which reduces bradykinin production, the experimental therapy is a bradykinin B2 receptor antagonist. This means it blocks the receptor through which bradykinin triggers swelling, regardless of how the signaling molecule is produced.
According to Pharvaris, this approach could help control attacks across different HAE types.
Experimental treatment met trial’s main goal
RAPIDe-3 included 10 adolescents and 124 adults, ages 12 to 75. Slightly more than half (57%) were female. Participants were randomly assigned to treat one attack with a 20 mg deucrictibant IR capsule and another with a placebo, or the reverse. Neither the participants nor the researchers knew which treatment was given.
Of the 134 participants, 113 treated at least one attack, for a total of 201 attacks. Most had HAE type 1 (102; 90%), followed by type 2 (eight; 7%). Two (2%) had the rarer type 3, while one (1%) had an unspecified type 1 or 2.
The main efficacy analysis included 88 participants who treated one attack with each option, allowing researchers to compare responses within the same participant.
Deucrictibant IR significantly outperformed placebo in shortening the time to symptom relief, meeting the trial’s main goal. Relief was defined as participants reporting that their symptoms felt at least a little better on two consecutive assessments.
The median time to initial relief was 1.28 hours with deucrictibant IR, compared with more than 12 hours with a placebo. Within four hours, 83% of evaluable attacks treated with deucrictibant had begun to improve, compared with 28% with a placebo.
Benefits generally consistent across age groups, HAE types
Deucrictibant IR also stopped attacks from worsening much sooner, after a median of 17.47 minutes, versus 228.67 minutes (nearly four hours) with a placebo. Substantial symptom relief and reductions in attack severity were likewise achieved significantly faster.
Complete symptom resolution took a median of 11.95 hours with deucrictibant IR, compared with more than 48 hours with a placebo. Within 24 hours, a single capsule achieved complete resolution without rescue medication in 60% of evaluable attacks, compared with 15% with a placebo.
Conventional rescue medication was used within 24 hours for 9% of deucrictibant-treated attacks versus 44% of placebo-treated attacks.
If approved, deucrictibant IR will be the first approved oral bradykinin B2 receptor antagonist, with the potential to address unmet needs of people living with HAE by providing reliable symptom relief and resolution with a single convenient oral capsule.
Benefits were generally consistent across age groups, HAE types, preventive treatment use, and attack severity and location, according to Pharvaris.
“The consistent results from RAPIDe-3 across subgroups underscores the clinical relevance of antagonizing the bradykinin B2 receptor, a downstream target that stops the effects of excess bradykinin regardless of the pathways through which it is generated,” said Peng Lu, MD, PhD, Pharvaris’ president.
Deucrictibant IR was generally well tolerated. Adverse events were reported in 24% of participants receiving deucrictibant and in 17% of those receiving a placebo. No treatment-related severe or serious adverse events occurred, and none led to treatment discontinuation.
“These results indicate that deucrictibant may help to address an unmet need for effective, well tolerated, oral options providing ease-of-administration, and rapid and sustained control of attack manifestations,” the researchers wrote.
An open-label extension study, RAPIDe-2 (NCT05396105), is ongoing to assess longer-term efficacy and safety of on-demand treatment with deucrictibant IR. An expanded access program (NCT07759141) also provides eligible U.S. patients with access to the treatment outside clinical trials.
According to Pharvaris, regulatory applications seeking approval of deucrictibant IR for on-demand HAE treatment are under review in the U.S. and Europe. A decision from the U.S. Food and Drug Administration is expected by April 23, 2027.
“If approved, deucrictibant IR will be the first approved oral bradykinin B2 receptor antagonist, with the potential to address unmet needs of people living with HAE by providing reliable symptom relief and resolution with a single convenient oral capsule,” Riedl added.
Leave a comment
Fill in the required fields to post. Your email address will not be published.